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# Septran (Co-Trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole. It is a folate antagonist that inhibits bacterial synthesis of tetrahydrofolate, a cofactor necessary for nucleic acid and protein synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea (enterotoxigenic E. coli)
## Adult Dosing
Dosing is typically based on the trimethoprim component. Standard adult dose for UTIs and most other indications: 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours.
* **UTIs:** 7-10 days for uncomplicated, 14 days for complicated.
* **PCP Treatment:** 15-20 mg/kg/day of trimethoprim divided into 3-4 doses for 14-21 days. Maximum 960 mg trimethoprim every 8 hours.
* **PCP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) once daily.
* **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 5 days.
* **Traveler's Diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 3-5 days.
## Pediatric Dosing
Dosing is based on age and indication. Trimethoprim component drives dosing.
* **UTIs:** 8 mg/kg/day of trimethoprim divided into two doses, given every 12 hours for 7-14 days.
* **PCP Treatment:** 15-20 mg/kg/day of trimethoprim divided into 3-4 doses, given every 6-8 hours for 14-21 days.
* **PCP Prophylaxis:** 150 mg/m²/day of trimethoprim orally divided into two doses, given every 12 hours, for 3 consecutive days per week.
Dosing for infants < 2 months is generally not recommended due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: Full dose.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Use with caution, or avoid. If used, give one-fourth the usual dose every 12 hours.
## Contraindications
* Documented hypersensitivity to trimethoprim or sulfonamides.
* Infants < 2 months of age (risk of kernicterus).
* Severe renal insufficiency when renal function cannot be monitored.
* Severe hepatic insufficiency.
* Megaloblastic anemia due to folate deficiency.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
* **Common:** Rash (especially in HIV patients), nausea, vomiting, diarrhea, pruritus.
* **Serious:** Severe cutaneous reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), hyperkalemia, bone marrow suppression (anemia, leukopenia, thrombocytopenia), hepatic damage, interstitial nephritis, crystalluria (ensure adequate hydration).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose as needed.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia. Monitor potassium levels.
* **Methotrexate:** Increased methotrexate levels and toxicity. Concomitant use generally avoided unless co-administered with leucovorin rescue.
* **Sulfonylureas:** Increased risk of hypoglycemia. Monitor blood glucose.
* **Potassium Supplements:** Increased risk of hyperkalemia.
## Monitoring
* Renal function (BUN, creatinine)
* Complete blood count (CBC) with differential, especially with prolonged therapy or in immunocompromised patients.
* Electrolytes (especially potassium).
* Liver function tests.
* Therapeutic drug monitoring is generally not required but may be considered in specific situations.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria.
* Rash is common, especially in HIV patients; monitor closely for signs of severe cutaneous reactions.
* Sulfonamide allergy does not necessarily preclude use in patients allergic to other sulfa-containing drugs (e.g., thiazide diuretics), but caution is advised.
* Consider folate supplementation (e.g., 5-10 mg daily) for patients on long-term therapy, especially those with risk factors for folate deficiency or receiving concomitant medications that interfere with folate metabolism.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and local institutional protocols for complete and definitive guidance.
